IL-4 is a pleiotropic cytokine primarily produced by activated T helper lymphocytes. It has been shown to have direct anti-tumor effects on human hematopoietic tumor cells and to inhibit the growth of tumor cells or to cause regression of established tumors in mice. The mechanism of these effects is not known, but interaction with the IL-4 receptor is the first step in the biological response. It has recently been shown that murine solid tumors express high affinity IL-4 receptors which are internalized after binding to ligand. We have used an antibody to recombinant IL-4 receptor to demonstrate the presence of IL-4 receptors on human malignant mesothelioma, neurofibrosarcoma and renal cell carcinoma. Primary cell cultures prepared from these human tumors also expressed IL-4 receptors. Flow cytometric analysis of renal cell carcinoma cells showed that almost all of the cells contain the receptor. These results show that human tumors express immunoreactive IL-4 receptors which may play a role in host immune response against cancers. Furthermore the receptors might be a target for diagnosis and therapy by an anti-IL-4 receptor antibody fused to toxins or radionuclides or alternatively by IL-4-toxins. This study is being extended to other human tumor types such as Kaposi's Sarcoma.